Nevirapine (NVP), tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC) is effective and well tolerated in naïve HIV-1 infected patients

Background: The combination of stavudine (d4T), 3TC and NVP was the WHO recommended first-line regimen for the treatment of naïve HIV-1 infected patients in resource-limited settings. But peripheral polyneuropathy, lipoatrophy and symptomatic hyperlactatemia are frequent and treatment-limiting adverse events associated with stavudine, especially when combined with antituberculous drugs. Tenofovir combined with lamivudine and efavirenz has proven excellent efficacy, but there is little experience when given with NVP. Methods: Retrospective analysis of all patients receiving TDF, NVP and 3TC or FTC as first-line treatment in the Frankfurt HIV cohort. Summary of results: 70 patients (15 female) with a median CD4 cell count of 210/μl (47–949) and HIV-RNA PCR of 140,000 copies/ml (2,500–2,000,000) at baseline received TDF, NVP and 3TC/FTC, and were treated for a median of 68 weeks (16–278). CD4 cells rose up to cells/μl 322 (119–1075) and 75% of the patients remained on treatment. All patients on treatment at week 48 were 100,000 c/m. Reasons for discontinuation (24%) were mainly adverse events (13%), with rash (7%) and liver toxicity (6%) being the two most common, whereas virologic failure, drug interaction and non-adherence were all relatively rare (each 3%). Conclusion: The combination of NVP, TDF and 3TC or FTC is effective and well tolerated in previously naïve HIV-1 infected patients even when started with low CD4 cell counts (100,000 c/ml). In the latest amendment of the WHO guidelines TDF, instead of d4T, is the recommended first-line treatment in resource-limited settings

Assessment of liver fibrosis and associated risk factors in HIV-infected individuals using transient elastography and serum biomarkers

Background: Liver fibrosis in human immunodeficiency virus (HIV)-infected individuals is mostly attributable to co-infection with hepatitis B or C. The impact of other risk factors, including prolonged exposure to combined antiretroviral therapy (cART) is poorly understood. Our aim was to determine the prevalence of liver fibrosis and associated risk factors in HIV-infected individuals based on non-invasive fibrosis assessment using transient elastography (TE) and serum biomarkers (Fibrotest [FT]). Methods: In 202 consecutive HIV-infected individuals (159 men; mean age 47 ± 9 years; 35 with hepatitis-C-virus [HCV] co-infection), TE and FT were performed. Repeat TE examinations were conducted 1 and 2 years after study inclusion. Results: Significant liver fibrosis was present in 16% and 29% of patients, respectively, when assessed by TE (≥ 7.1 kPa) and FT (> 0.48). A combination of TE and FT predicted significant fibrosis in 8% of all patients (31% in HIV/HCV co-infected and 3% in HIV mono-infected individuals). Chronic ALT, AST and γ-GT elevation was present in 29%, 20% and 51% of all cART-exposed patients and in 19%, 8% and 45.5% of HIV mono-infected individuals. Overall, factors independently associated with significant fibrosis as assessed by TE (OR, 95% CI) were co-infection with HCV (7.29, 1.95-27.34), chronic AST (6.58, 1.30-33.25) and γ-GT (5.17, 1.56-17.08) elevation and time on dideoxynucleoside therapy (1.01, 1.00-1.02). In 68 HIV mono-infected individuals who had repeat TE examinations, TE values did not differ significantly during a median follow-up time of 24 months (median intra-patient changes at last TE examination relative to baseline: -0.2 kPa, p = 0.20). Conclusions: Chronic elevation of liver enzymes was observed in up to 45.5% of HIV mono-infected patients on cART. However, only a small subset had significant fibrosis as predicted by TE and FT. There was no evidence for fibrosis progression during follow-up TE examinations

Virological and immunological response to three boosted protease inhibitor regimens

Poster presentation: Purpose of the study To compare the virological, immunological and clinical response to three boosted double protease inhibitor (PI) regimens of saquinavir and ritonavir in combination with lopinavir (LOPSAQ), atazanavir (ATSAQ) or fosamprenavir (FOSAQ) without reverse transcriptase inhibitors (RTI) in HIV-positive patients with limited RTI treatment options. ..

Persistence of HCV in acutely-infected patients depletes C24-ceramide and upregulates sphingosine and sphinganine serum levels

Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance. Quantification of serum sphingolipids was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spontaneous clearance was observed in 11 out of 60 patients (18.3%), a sustained viral response (SVR) in 43 out of 45 patients (95.5%) receiving an antiviral treatment after follow-up, whereas persistence of HCV occurred in six out of 60 patients (10%). C24-ceramide (C24-Cer)-levels increased at follow-up in patients with spontaneous HCV eradication (p < 0.01), as compared to baseline. Sphingosine and sphinganine values were significantly upregulated in patients unable to clear HCV over time compared to patients with spontaneous clearance of HCV infection on follow-up (p = 0.013 and 0.006, respectively). In summary, the persistence of HCV after acute infection induces a downregulation of C24Cer and a simultaneous elevation of serum sphingosine and sphinganine concentrations

Expanding epidemic of recently acquired HCV in HIV-coinfected patients over a period of 10 years

Background &amp; Aims: Ongoing transmission of HCV infections is associated with risk factors such as drug injection, needlestick injuries, and men who have sex with men (MSM). Ways of transmission, the course of acute infection, changes of virologic features, and incidence over time are not well known. Methods: Over a period of 10 years, n = 161 patients with recently acquired HCV infection (RAHC) (median follow-up 6.8 years) were prospectively enrolled. NS5B sequencing was performed to re-evaluate the HCV genotype (GT) and for phylogenetic analyses. Results: Patients with RAHC were mainly male (92.5%), MSM (90.1%), and HIV-coinfected (86.3%). Transmission risk factors for MSM and non-MSM were sexual risk behaviour (100 and 6.3%, respectively), injection drug use (9.7 and 37.5%, respectively), and nasal drug use (15.2 and 0%, respectively). Spontaneous and interferon- or direct-acting antiviral-based clearance rates were 13.6, 84.3 and 93.4%, respectively. Mean RAHC declined from 19.8 in the first to 13.2 in the past five study years. Although the majority of infections was caused by HCV GT1a, the frequency of HCV GT4d and slightly HCV GT3a increased over time. No relevant clustering of HCV isolates was observed in non-MSM. However, 45% of HCV GT1a and 100% of HCV GT4d MSM cases clustered with MSM isolates from other countries. Travel-associated infections were supported by personal data in an MSM subgroup. No international clustering was detected in MSM with HCV GT1b or HCV GT3a. Conclusions: RAHCs were mainly diagnosed in HIV-coinfected MSM patients and were associated with sexual risk behaviour. Spontaneous clearance rates were low, and phylogenetic clusters were observed in the majority of patients. Impact and Implications: We evaluated the occurrence and transmission of recently acquired HCV infections (RAHCs) over a period of 10 years. Our data demonstrate that the presence of RAHC was mainly found in HIV-coinfected MSM, with internationally connected transmission networks being observed in the majority of patients. Spontaneous clearance rates were low, and reinfection rates increased mainly driven by a small subset of MSM patients with high-risk behaviour